Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope

Non-centrosomal microtubule-organizing centers (MTOCs) are pivotal for the function of multiple cell types, but the processes initiating their formation are unknown. Here, we find that the transcription factor myogenin is required in murine myoblasts for the localization of MTOC proteins to the nucl...

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Autores principales:	Robert Becker, Silvia Vergarajauregui, Florian Billing, Maria Sharkova, Eleonora Lippolis, Kamel Mamchaoui, Fulvia Ferrazzi, Felix B Engel
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	centrosome MTOC myogenin microtubules muscle differentiation AKAP6 Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d9441490c18344098f6e6fe8eafb87b5
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spelling	oai:doaj.org-article:d9441490c18344098f6e6fe8eafb87b52021-11-15T05:38:40ZMyogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope10.7554/eLife.656722050-084Xe65672https://doaj.org/article/d9441490c18344098f6e6fe8eafb87b52021-10-01T00:00:00Zhttps://elifesciences.org/articles/65672https://doaj.org/toc/2050-084XNon-centrosomal microtubule-organizing centers (MTOCs) are pivotal for the function of multiple cell types, but the processes initiating their formation are unknown. Here, we find that the transcription factor myogenin is required in murine myoblasts for the localization of MTOC proteins to the nuclear envelope. Moreover, myogenin is sufficient in fibroblasts for nuclear envelope MTOC (NE-MTOC) formation and centrosome attenuation. Bioinformatics combined with loss- and gain-of-function experiments identified induction of AKAP6 expression as one central mechanism for myogenin-mediated NE-MTOC formation. Promoter studies indicate that myogenin preferentially induces the transcription of muscle- and NE-MTOC-specific isoforms of Akap6 and Syne1, which encodes nesprin-1α, the NE-MTOC anchor protein in muscle cells. Overexpression of AKAP6β and nesprin-1α was sufficient to recruit endogenous MTOC proteins to the nuclear envelope of myoblasts in the absence of myogenin. Taken together, our results illuminate how mammals transcriptionally control the switch from a centrosomal MTOC to an NE-MTOC and identify AKAP6 as a novel NE-MTOC component in muscle cells.Robert BeckerSilvia VergarajaureguiFlorian BillingMaria SharkovaEleonora LippolisKamel MamchaouiFulvia FerrazziFelix B EngeleLife Sciences Publications LtdarticlecentrosomeMTOCmyogeninmicrotubulesmuscle differentiationAKAP6MedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	centrosome MTOC myogenin microtubules muscle differentiation AKAP6 Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	centrosome MTOC myogenin microtubules muscle differentiation AKAP6 Medicine R Science Q Biology (General) QH301-705.5 Robert Becker Silvia Vergarajauregui Florian Billing Maria Sharkova Eleonora Lippolis Kamel Mamchaoui Fulvia Ferrazzi Felix B Engel Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope
description	Non-centrosomal microtubule-organizing centers (MTOCs) are pivotal for the function of multiple cell types, but the processes initiating their formation are unknown. Here, we find that the transcription factor myogenin is required in murine myoblasts for the localization of MTOC proteins to the nuclear envelope. Moreover, myogenin is sufficient in fibroblasts for nuclear envelope MTOC (NE-MTOC) formation and centrosome attenuation. Bioinformatics combined with loss- and gain-of-function experiments identified induction of AKAP6 expression as one central mechanism for myogenin-mediated NE-MTOC formation. Promoter studies indicate that myogenin preferentially induces the transcription of muscle- and NE-MTOC-specific isoforms of Akap6 and Syne1, which encodes nesprin-1α, the NE-MTOC anchor protein in muscle cells. Overexpression of AKAP6β and nesprin-1α was sufficient to recruit endogenous MTOC proteins to the nuclear envelope of myoblasts in the absence of myogenin. Taken together, our results illuminate how mammals transcriptionally control the switch from a centrosomal MTOC to an NE-MTOC and identify AKAP6 as a novel NE-MTOC component in muscle cells.
format	article
author	Robert Becker Silvia Vergarajauregui Florian Billing Maria Sharkova Eleonora Lippolis Kamel Mamchaoui Fulvia Ferrazzi Felix B Engel
author_facet	Robert Becker Silvia Vergarajauregui Florian Billing Maria Sharkova Eleonora Lippolis Kamel Mamchaoui Fulvia Ferrazzi Felix B Engel
author_sort	Robert Becker
title	Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope
title_short	Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope
title_full	Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope
title_fullStr	Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope
title_full_unstemmed	Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope
title_sort	myogenin controls via akap6 non-centrosomal microtubule-organizing center formation at the nuclear envelope
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/d9441490c18344098f6e6fe8eafb87b5
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_version_	1718428585599959040

Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope

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